Patent DE-102006050515-A1 (DE)
Title: New substituted dipyridiyl-dihydropyrazolone derivatives are hypoxia-inducible transcription factor-prolyl-4-hydroxylase inhibitors useful to treat/prevent e.g. cardiovascular diseases, heart-circulation diseases, heart failure and anemia
Inventor: THEDE KAI
IPC: A61P7/06
Filed: 2006-10-26
Abstract: Substituted dipyridiyl-dihydropyrazolone derivatives (I) or their salts, solvates and solvate of salts, are new. Substituted dipyridiyl-dihydropyrazolone derivatives of formula (I) or their salts, solvates and solvate of salts, are new. A : CH or N; R 1>, R 2>(1-6C)-alkyl, (1-6C)-alkoxy (both substituted with 1-3 of halo, CN, oxo, OH, NH 2, hydroxycarbonyl, aminocarbonyl, (3-7C)-cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl, -C(=O)-R 4>, -C(=O)-OR 5>, -C(=O)-NR 6>R 7>, -O-C(=O)-R 8>, -O-C(=O)-NR 9>R 1> 0>, -NR 1> 1>-C(=O)-R 1> 2>, -NR 1> 3>-C(=O)-OR 1> 4>, -NR 1> 5>-C(=O)-NR 1> 6>R 1> 7>, -NR 1> 8>-SO 2-R 1> 9>, -SO 2-R 2> 0>, -SO 2-NR 2> 1>R 2> 2>, -OR 2> 3>, -SR 2> 4> or -NR 2> 5>R 2> 6>, (where the (hetero)cycloalkyl, phenyl or heteroaryl is optionally substituted with halo, CN, (1-4C)-alkyl, CF 3, OH, (1-4C)-alkoxy, trifluoromethoxy, oxo, amino, mono-(1-4C)-alkylamino, di-(1-4C)-alkylamino, hydroxycarbonyl or (1-4C)-alkoxycarbonyl), (3-7C)-cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl (where the (hetero)cycloalkyl, phenyl or heteroaryl is optionally substituted with 1-3 of (1-6C)-alkyl, halo, CN, oxo, NH 2, hydroxycarbonyl, aminocarbonyl, -C(=O)-R 4>, -C(=O)-OR 5>, -C(=O)-NR 6>R 7>, -O-C(=O)-R 8>, -O-C(=O)-NR 9>R 1> 0>, -NR 1> 1>-C(=O)-R 1> 2>, -NR 1> 3>-C(=O)-OR 1> 4>, -NR 1> 5>-C(=O)-NR 1> 6>R 1> 7>, -NR 1> 8>-SO 2-R 1> 9>, -SO 2-R 2> 0>, -SO 2-NR 2> 1>R 2> 2>, -OR 2> 3>, -SR 2> 4> or -NR 2> 5>R 2> 6>, where the alkyl is optionally substituted with halo, CN, OH, trifluoromethoxy, (1-4C)-alkoxy, amino, mono-(1-4C)-alkylamino, di-(1-4C)-alkylamino, hydroxycarbonyl, (1-4C)-alkoxycarbonyl, (3-7C)-cycloalkyl, 4-7 membered heterocycloalkyl, phenyl or 5- or 6-membered heteroaryl), halo, CN, NO 2, OH, NH 2, hydroxycarbonyl, aminocarbonyl, -C(=O)-R 4>, -C(=O)-OR 5>, -C(=O)-NR 6>R 7>, -O-C(=O)-R 8>, -O-C(=O)-NR 9>R 1> 0>, -NR 1> 1>-C(=O)-R 1> 2>, -NR 1> 3>-C(=O)-OR 1> 4>, -NR 1> 5>-C(=O) -NR 1> 6>R 1> 7>, -NR 1> 8>-SO 2-R 1> 9>, -SO 2-R 2> 0>, -SO 2-NR 2> 1>R 2> 2>, -OR 2> 3>, -SR 2> 4> or -NR 2> 5>R 2> 6>; either R 4>-R 6>, R 8>, R 9>, R 1> 2>, R 1> 4>, R 1> 6>, R 1> 9>-R 2> 5>(3-7C)-cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 5- or 6-membered heteroaryl (all optionally substituted with halo, CN, (1-4C)-alkyl, trifluoromethyl, OH, (1-4C)-alkoxy, trifluoromethoxy, oxo, amino, mono-(1-4C)-alkylamino, di-(1-4C)-alkylamino, hydroxycarbonyl or (1-4C)-alkoxycarbonyl) or (1-6C)-alkyl (optionally substituted with1-3 of halo, CN, OH, trifluoromethoxy, (1-4C)-alkoxy, amino, mono-(1-4C)-alkylamino, di-(1-4C)-alkylamino, hydroxycarbonyl, (1-4C)-alkoxycarbonyl, (3-7C)-cycloalkyl, 4-7 membered heterocycloalkyl, phenyl or 5- or 6-membered heteroaryl); and R 7>, R 1> 0>, R 1> 1>, R 1> 3>, R 1> 5>, R 1> 7>, R 1> 8>, R 2> 2>, R 2> 6>H or (1-6C)-alkyl (optionally substituted with 1-3 of halo, CN, OH, trifluoromethoxy, (1-4C)-alkoxy, amino, mono-(1-4C)-alkylamino, di-(1-4C)-alkylamino, hydroxycarbonyl or (1-4C)-alkoxycarbonyl); or R 6>R 7>, R 9>R 1> 0>, R 1> 1>R 1> 2>, R 1> 3>R 1> 4>, R 1> 5>R 1> 6>, R 1> 6>R 1> 7>, R 1> 8>R 1> 9>, R 2> 1>R 2> 2>, R 2> 5>R 2> 6>5- or 6-membered heterocycloalkyl ring (optionally substituted with 1-3 of halo, CN, (1-4C)-alkyl, trifluoromethyl, OH, (1-4C)-alkoxy, trifluoromethoxy, oxo, amino, mono-(1-4C)-alkylamino, di-(1-4C)-alkylamino, hydroxycarbonyl or (1-4C)-alkoxycarbonyl); R 3>H, (1-6C)-alkyl or (3-7C)-cycloalkyl; and m, n : 0-3. Independent claims are included for: (1) the preparations of (I); and (2) a medicament comprising (I) and inert, non-toxic auxiliary material. [Image] ACTIVITY : Cardiovascular-Gen; Cardiant; Antianemic; Nephrotropic; Antianginal; Cerebroprotective; Vasotropic; Antiarteriosclerotic; Hypotensive; Respiratory-Gen; Antiarthritic; Antirheumatic; Ophthalmological; Antiparkinsonian; Neuroprotective; Nootropic; Analgesic; Vulnerary; Anabolic; Endocrine-Gen; Antidiabetic; Antimicrobial; Antiinflammatory. MECHANISM OF ACTION : Hypoxia-inducible transcription factor (HIF)-prolyl-4-hydroxylase inhibitor.